Mechanism of inhibition of rat liver mitochondrial respiration by oxmetidine, an H sub(2)-receptor antagonist

In isolated rat liver mitochondria (RLM), oxmetidine inhibits pyruvate/malate- but not succinate-supported, ADP-stimulated oxygen consumption (state 3). The purpose of this investigation was to determine the exact molecular site of oxmetidine-induced inhibition of RLM electron transport. Oxmetidine...

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Published inThe Journal of pharmacology and experimental therapeutics Vol. 252; no. 3; pp. 908 - 914
Main Authors Hoke, G D, Cheng, Hung-Yuan, Mirabelli, C K, Rush, G F
Format Journal Article
LanguageEnglish
Published 01.01.1990
Subjects
liver
mitochondria
respiration
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Summary:In isolated rat liver mitochondria (RLM), oxmetidine inhibits pyruvate/malate- but not succinate-supported, ADP-stimulated oxygen consumption (state 3). The purpose of this investigation was to determine the exact molecular site of oxmetidine-induced inhibition of RLM electron transport. Oxmetidine did not significantly inhibit succinate-supported, ADP-stimulated state 3 oxygen consumption in isolated RLM at concentrations up to 0.5 mM. In contrast, oxmetidine significantly inhibited beta-hydroxybutyrate- or isocitrate-supported mitochondrial state 3 oxygen consumption at concentrations above 10 mu M and 25 mu M, respectively. The studies suggest that oxmetidine may inhibit mitochondrial electron transport by "short circuiting" the flow of electrons between NADH dehydrogenase and ubiquinone.
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SourceType-Scholarly Journals-1
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ISSN:0022-3565